How to manage a patient with hyperkalemia on lisinopril?

Management of Hyperkalemia (K+ 5.7 mEq/L) in a Patient on Lisinopril

Do not discontinue lisinopril immediately—instead, implement strategies to lower potassium while maintaining this life-saving medication whenever possible. 1

Immediate Assessment

• Obtain an ECG immediately to assess for cardiac manifestations of hyperkalemia (peaked T waves, flattened P waves, prolonged PR interval, widened QRS complex), as these findings indicate urgent treatment regardless of the exact potassium value 2, 3
• Verify the result is not pseudohyperkalemia from hemolysis, repeated fist clenching, or poor phlebotomy technique before initiating aggressive treatment 2, 3
• Assess for symptoms including muscle weakness, paresthesias, or palpitations, though symptoms are typically nonspecific at this level 2

Risk Stratification

At K+ 5.7 mEq/L, this represents moderate hyperkalemia (5.5-6.0 mEq/L range) 2, 3. The FDA label for lisinopril specifically warns that hyperkalemia occurred in 2.2% of hypertensive patients and 4.8% of heart failure patients, with risk factors including renal insufficiency, diabetes mellitus, and concomitant use of potassium-sparing diuretics or potassium supplements 4.

Treatment Algorithm

Step 1: Medication Review and Adjustment (First Priority)

Review and eliminate contributing medications: 2, 3

• Stop NSAIDs immediately if the patient is taking them, as they impair renal potassium excretion and attenuate diuretic effects 1, 4
• Discontinue potassium supplements and salt substitutes containing potassium 2, 4
• Hold potassium-sparing diuretics (spironolactone, amiloride, triamterene) if prescribed 4
• Review other contributing medications: trimethoprim, heparin, beta-blockers 2

Regarding lisinopril specifically:

• Temporarily reduce the lisinopril dose by 50% rather than stopping it completely 1
• The 2025 American Journal of Kidney Diseases guidelines emphasize that GDMT withdrawal is associated with poorer clinical outcomes, so we should try hard not to stop or to quickly restart GDMT whenever possible 1

Step 2: Add an SGLT2 Inhibitor (Preferred Strategy)

Initiate an SGLT2 inhibitor (dapagliflozin, empagliflozin, or canagliflozin) together with continued lisinopril therapy 1. This is the best answer based on the 2025 AJKD Core Curriculum case scenario that mirrors this clinical situation 1:

• SGLT2 inhibitors reduced the risk of serious hyperkalemia by 16% (hazard ratio 0.84; 95% CI, 0.76–0.93) in patients taking RAAS inhibitors 1
• This strategy allows simultaneous maintenance of GDMT to improve both cardiovascular and kidney outcomes 1
• SGLT2 inhibitors provide additional benefits beyond potassium management in patients with CKD, heart failure, or diabetes 1

Step 3: Consider Switching to Sacubitril/Valsartan (Alternative Strategy)

If the patient has heart failure with reduced ejection fraction, consider switching from lisinopril to sacubitril/valsartan 1:

• In the PARADIGM-HF trial, severe hyperkalemia was 37% less common with sacubitril/valsartan compared to enalapril (hazard ratio 1.37 for enalapril; 95% CI, 1.06-1.76) 1
• This applies specifically to patients with symptomatic HFrEF treated with mineralocorticoid receptor antagonists 1

Step 4: Initiate a Potassium Binder (If Needed)

If potassium remains >5.0 mEq/L despite the above interventions, add a newer potassium binder 1, 2:

Preferred agents:

• Sodium zirconium cyclosilicate (SZC/Lokelma): 10 g three times daily for 48 hours, then 5-15 g once daily for maintenance; onset of action ~1 hour 2
• Patiromer (Veltassa): 8.4 g once daily with food, titrated up to 25.2 g daily; onset of action ~7 hours 2

Avoid sodium polystyrene sulfonate (Kayexalate) due to risk of bowel necrosis and lack of efficacy data 1, 2

Step 5: Enhance Renal Potassium Excretion

If the patient has adequate kidney function (eGFR >30 mL/min), add or increase loop diuretics 2:

• Furosemide 40-80 mg daily to increase urinary potassium excretion 2
• Titrate to maintain euvolemia, not primarily for potassium management 2

Step 6: Dietary Modification

Restrict dietary potassium to <3 grams/day (approximately 50-70 mmol/day) 3:

• Avoid high-potassium foods: bananas, oranges, potatoes, tomatoes, legumes, chocolate, yogurt 3
• Avoid salt substitutes containing potassium 3
• Avoid herbal supplements that raise potassium (alfalfa, dandelion, horsetail, nettle) 2

Monitoring Protocol

Check potassium and renal function within 7-10 days after implementing these interventions 1, 2:

• Continue monitoring every 1-2 weeks until values stabilize 2
• Then check at 3 months, subsequently every 6 months 2
• More frequent monitoring is required if the patient has CKD, diabetes, or heart failure 2

When to Escalate Care

Discontinue or further reduce lisinopril only if: 1

• Potassium rises to >6.5 mEq/L despite the above interventions 1
• ECG changes develop 2, 3
• Patient develops symptoms of severe hyperkalemia 3

If lisinopril must be stopped temporarily:

• Restart at a lower dose once potassium <5.0 mEq/L 2
• Maintain concurrent potassium binder therapy 2
• Simple rechallenge with the same or lower dose remains feasible—in the DIAMOND trial, >80% of patients in the placebo group did not develop recurrent hyperkalemia 1

Critical Pitfalls to Avoid

• Never permanently discontinue lisinopril due to moderate hyperkalemia without attempting the strategies above, as RAAS inhibitors provide mortality benefit in cardiovascular and renal disease 1, 2
• Do not ignore the need for repeat potassium measurement to confirm hyperkalemia and monitor treatment response 3
• Do not delay treatment while waiting for repeat lab confirmation if ECG changes are present—ECG changes indicate urgent need regardless of the exact potassium value 2
• Avoid combining lisinopril with other RAAS inhibitors (ARBs, aliskiren, or dual MRA therapy), as this markedly increases hyperkalemia risk without proven benefit 4, 5